Registro completo de metadatos
| Campo DC | Valor | Lengua/Idioma |
|---|---|---|
| dc.provenance | CONICET | - |
| dc.creator | Rigalli, Juan Pablo | - |
| dc.creator | Perdomo, Virginia | - |
| dc.creator | Luquita, Marcelo Gabriel | - |
| dc.creator | Villanueva, Silvina Stella Maris | - |
| dc.creator | Arias, Agostina | - |
| dc.creator | Theile, Dirk | - |
| dc.creator | Weiss, Johanna | - |
| dc.creator | Mottino, Aldo Domingo | - |
| dc.creator | Ruiz, Maria Laura | - |
| dc.creator | Catania, Viviana Alicia | - |
| dc.date | 2017-04-18T19:09:10Z | - |
| dc.date | 2017-04-18T19:09:10Z | - |
| dc.date | 2012-12 | - |
| dc.date | 2017-04-18T14:03:27Z | - |
| dc.date.accessioned | 2019-04-29T15:44:25Z | - |
| dc.date.available | 2019-04-29T15:44:25Z | - |
| dc.date.issued | 2017-04-18T19:09:10Z | - |
| dc.date.issued | 2017-04-18T19:09:10Z | - |
| dc.date.issued | 2012-12 | - |
| dc.date.issued | 2017-04-18T14:03:27Z | - |
| dc.identifier | Rigalli, Juan Pablo; Perdomo, Virginia; Luquita, Marcelo Gabriel; Villanueva, Silvina Stella Maris; Arias, Agostina; et al.; Regulation of biotransformation systems and ABC transporters by Benznidazole in HepG2 cells: involvement of Pregnane X-Receptor; Public Library Of Science; Neglected Tropical Diseases; 6; 12; 12-2012; 1-10; e1951 | - |
| dc.identifier | 1935-2727 | - |
| dc.identifier | http://hdl.handle.net/11336/15392 | - |
| dc.identifier | 1935-2735 | - |
| dc.identifier.uri | http://rodna.bn.gov.ar:8080/jspui/handle/bnmm/300783 | - |
| dc.description | Background: Benznidazole (BZL) is the only antichagasic drug available in most endemic countries. Its effect on the expression and activity of drug-metabolizing and transporter proteins has not been studied yet. Methodology/Principal Findings: Expression and activity of P-glycoprotein (P-gp), Multidrug resistance-associated protein 2 (MRP2), Cytochrome P450 3A4 (CYP3A4), and Glutathione S-transferase (GST) were evaluated in HepG2 cells after treatment with BZL. Expression was estimated by immunoblotting and real time PCR. P-gp and MRP2 activities were estimated using model substrates rhodamine 123 and dinitrophenyl-S-glutathione (DNP-SG), respectively. CYP3A4 and GST activities were evaluated through their abilities to convert proluciferin into luciferin and 1-chloro-2,4-dinitrobenzene into DNP-SG, respectively. BZL (200 µM) increased the expression (protein and mRNA) of P-gp, MRP2, CYP3A4, and GSTπ class. A concomitant enhancement of activity was observed for all these proteins, except for CYP3A4, which exhibited a decreased activity. To elucidate if pregnane X receptor (PXR) mediates BZL response, its expression was knocked down with a specific siRNA. In this condition, the effect of BZL on P-gp, MRP2, CYP3A4, and GSTπ protein up-regulation was completely abolished. Consistent with this, BZL was able to activate PXR, as detected by reporter gene assay. Additional studies, using transporter inhibitors and P-gp-knock down cells, demonstrated that P-gp is involved in BZL extrusion. Pre-treatment of HepG2 cells with BZL increased its own efflux, as a consequence of P-gp up-regulation. Conclusions/Significance: Modifications in the activity of biotransformation and transport systems by BZL may alter the pharmacokinetics and efficiency of drugs that are substrates of these systems, including BZL itself. | - |
| dc.description | Fil: Rigalli, Juan Pablo. Universität Heidelberg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | - |
| dc.description | Fil: Perdomo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | - |
| dc.description | Fil: Luquita, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | - |
| dc.description | Fil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | - |
| dc.description | Fil: Arias, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | - |
| dc.description | Fil: Theile, Dirk. Universität Heidelberg; Alemania | - |
| dc.description | Fil: Weiss, Johanna. Universität Heidelberg; Alemania | - |
| dc.description | Fil: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | - |
| dc.description | Fil: Ruiz, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | - |
| dc.description | Fil: Catania, Viviana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | - |
| dc.format | application/pdf | - |
| dc.format | application/pdf | - |
| dc.language | eng | - |
| dc.publisher | Public Library Of Science | - |
| dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pntd.0001951 | - |
| dc.relation | info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001951 | - |
| dc.relation | info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521711/ | - |
| dc.rights | info:eu-repo/semantics/openAccess | - |
| dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | - |
| dc.source | reponame:CONICET Digital (CONICET) | - |
| dc.source | instname:Consejo Nacional de Investigaciones Científicas y Técnicas | - |
| dc.source | instacron:CONICET | - |
| dc.source.uri | http://hdl.handle.net/11336/15392 | - |
| dc.subject | BENZNIDAZOLE | - |
| dc.subject | PXR | - |
| dc.subject | HepG2 | - |
| dc.subject | MRP-2 | - |
| dc.subject | Farmacología y Farmacia | - |
| dc.subject | Medicina Básica | - |
| dc.subject | CIENCIAS MÉDICAS Y DE LA SALUD | - |
| dc.title | Regulation of biotransformation systems and ABC transporters by Benznidazole in HepG2 cells: involvement of Pregnane X-Receptor | - |
| dc.type | info:eu-repo/semantics/article | - |
| dc.type | info:eu-repo/semantics/publishedVersion | - |
| dc.type | info:ar-repo/semantics/articulo | - |
| Aparece en las colecciones: | CONICET | |
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